State-of-the-Science Workshop Report: Issues and Approaches in Low Dose–response Extrapolation for Environmental Health Risk Assessment

Low-dose extrapolation model selection for evaluating the health effects of environmental pollutants is a key component of the risk assessment process. At a workshop held in Baltimore, MD, on April 23-24, 2007, and sponsored by U.S. Environmental Protection Agency (EPA) and Johns Hopkins Risk Sciences and Public Policy Institute, a multidisciplinary group of experts reviewed the state of the science regarding low-dose extrapolation modeling and its application in environmental health risk assessments. Discussion topics were identified based on a literature review, which included examples for which human responses to ambient exposures have been extensively characterized for cancer and/or noncancer outcomes.
Topics included:
  • the need for formalized approaches and criteria to assess the evidence for mode of action;
  • the use of human vs. animal data;
  • the use of mode of action information in biologically-based models; and
  • the implications of interindividual variability, background disease processes and background exposures in threshold vs. nonthreshold model choice.
Approaches that differ from current practice were recommended for extrapolating high-dose animal data to low-dose human exposures, including categorical approaches for integrating information on mode of action, statistical approaches such as model averaging, and inference-based models that explicitly consider uncertainty and interindividual variability.

Workshop goals were to: (1) review the state of the science for high-to-low dose-response extrapolation methods in environmental health risk assessments, (2) identify realistic approaches for the practical application of low-dose extrapolation incorporating the relevant scientific evidence to the fullest extent feasible and (3) identify areas for future work.


This is the final report.


White, R. H., I. L. COTE, L. Zeise, M. Fox, F. Dominici, T. A. Burke, P. WHITE, D. HATTIS, AND J. M. Sarnet. State-of-the-Science Workshop Report: Issues and Approaches in Low Dose–response Extrapolation for Environmental Health Risk Assessment. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 117(2):283-7, (2009).

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